Tmem41b-flox Mouse

TMEM41B, also known as Stasimon, is an endoplasmic reticulum (ER)-localized transmembrane protein with phospholipid scrambling activity. It is involved in multiple essential biological processes, including lipoprotein biogenesis, lipid homeostasis, autophagosome formation, and plays a significant role in various viral infections. It has been associated with pathways related to lipid metabolism and autophagy, and its function is crucial for maintaining cellular and organismal fitness [2,4,5,6,7,8,9]. Genetic models, such as KO and CKO mouse models, have been valuable in studying its functions.

Full-genome loss-of-function CRISPR-Cas9 screens identified TMEM41B as a pan-flavivirus host factor. It is required for the infection of all tested Flaviviridae family members and SARS-CoV-2 of the Coronaviridae family. Single nucleotide polymorphisms present in nearly 20% of East Asian populations reduce flavivirus infection. Mechanistically, TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature for viral genome replication [1]. In β -coronavirus infection, TMEM41B is essential for double-membrane vesicle (DMV) formation. In TMEM41B KO cells, the interaction between viral non-structural proteins nsp3 and nsp4 is reduced, suppressing DMV formation [3]. Hepatic TMEM41B loss eliminates plasma lipids due to the absence of mature lipoproteins in the ER but paradoxically activates lipid production, leading to non-alcoholic hepatosteatosis in TMEM41B -deficient mice [2]. Also, TMEM41B knockdown suppresses Pseudorabies virus (PRV) proliferation by affecting PRV entry and lipid -regulated clathrin -coated pits dynamics [7]. Postnatal depletion of TMEM41B in a CKO mouse model arrests weight gain, causes motor dysfunction, and leads to death, and it severely affects cell proliferation in mouse embryonic fibroblasts [8].

In conclusion, TMEM41B is a multifunctional protein essential for processes like lipoprotein biogenesis, lipid homeostasis, and autophagosome formation. Its role in facilitating viral infections, especially those of flaviviruses and coronaviruses, has been well -demonstrated through KO/CKO mouse models. These models have also shown its importance in lipid -related diseases such as non -alcoholic hepatosteatosis and in the context of viral diseases like PRV infection, providing potential therapeutic targets for these conditions.